脓毒症相关生物标志物及作用机制研究进展

脓毒症是临床中常见的一种危重症感染导致的多器官功能障碍综合征, 也是临床中常见的患者死亡的主要原因之一, 具有高发病率、高病死率的特点, 尽管现在抗生素利用和生命支持方面有了很大的改善, 但是脓毒症患者病死率仍居高不下, 早期识别脓毒症生物标志物变化, 对脓毒症治疗提供思路、判断患者预后有很大益处。     

血必净联合应用乌司他丁对降低脓毒性休克病死率的价值

严重脓毒症是急诊重症监护病室（emergency intensive careuni,t EICU）常见的急危重症之一,因其来势凶猛、进展迅速、病死率高,目前得到了医学界广泛的关注.本文回顾性分析了我院MICU收治的严重脓毒症患者的临床资料.     

小儿脓毒症28例观察及护理

脓毒症是目前危重医学所面临的主要问题,尽管抗感染治疗和生命支持技术取得了很大进步,但脓毒症发病率和病死率仍居高不下[1],小儿脓毒症更是起病急、病情进展快、病死率高。我院重症监护病房(PICU)2004年5月至2007年5月收住了脓毒症患儿28例,报告如下。1临床资料1.1一般资料28     

脓毒症中线粒体DNA 的研究进展

脓毒症是重症监护病房常见急危重症,发病率、病死率均较高,早期识别困难,临床医师若不能在早期及时识别及救治脓毒症患者,可进一步发展为脓毒症休克、多脏器功能 衰竭 ,从而增加病死率。近年来,有研究表明线粒体损伤与脓毒症发生发展密切相关,而线粒体DNA(mtDNA)损伤是线粒体损伤重要机制之一。“危险模型”提出,当细胞受到损害时,无论刺激的性质和强度,细胞均会将其组分释放到细胞外空间,驱动免疫或炎症反应,这类内源性分子被称为DAMP。mtDNA 作为一种DAMP,在脓毒症中可能通过Toll 样受体9(TLR9)和炎性小体影响机体炎症反应,为mtDNA 作为脓毒症诊断的新生物学标记提供了可能。脓毒症患者体内游离mtDNA 异常升高可能与患者病死率显著相关,本文就近年来脓毒症中mtDNA 研究进展作一综述     

中药有效成分治疗脓毒症的研究进展

脓毒症是指由感染引起的全身性炎症反应,是严重感染、重度创伤或烧伤、外科手术后常见的并发症,患病率高、病死率高,没有特效药物,是世界性医学难题.近年来的临床和实验研究发现,多个中药单体成分在治疗脓毒症方面有一定的效果.将治疗脓毒症的有效成分根据其化学结构进行分类,综述近年来中药有效成分在治疗脓毒症方面的研究进展,为进一步研究与开发治疗脓毒症的新药提供思路和参考.     

N-乙酰半胱氨酸防治脓毒症的研究进展

脓毒症是临床常见危重症,病死率高,其发病机制复杂,目前认为氧化应激参与其发病过程,N-乙酰半胱氨酸作为一种巯基供给体,具有抗氧化损伤,抗炎等作用,日益受到重视。现就脓毒症的发病机制、N-乙酰半胱氨酸防治脓毒症的机制及其在动物实验和临床应用中的情况作一介绍。     

血必净注射液治疗脓毒症52例临床分析

脓毒症是内外科危重患者的常见并发症,进一步发展可导致脓毒症休克、多器官功能障碍综合征。据报道,全世界每年大约10万人口中有50～300例脓毒症病例,且每年以1．5％～8．0％的速度增加,脓毒症病情凶险,病死率高达30％～50％。     

连续性血液净化治疗小儿重度脓毒血症的护理

脓毒血症主要是指一种由感染诱发的全身性炎性反应中产生的病理损伤引起的临床综合征,是一种十分常见但治疗困难的综合征[1]。在2012国际严重脓毒症和脓毒症休克治疗指南(SSC)中指出重度脓毒血症是指脓毒症伴有器官功能障碍、组织灌注不良或低血压。儿科脓毒症患病率高,病死率高,治疗费用昂贵,随着近年来医学研究的新进展,连续性血液净化在脓毒血症病人的抢救中效果较好,提升了这一疾病的抢救成     

脓毒症的流行病学研究进展

脓毒症（sepsis）是创伤、烧伤、休克、感染等临床急危重病患者的常见严重并发症之一，一份来自北美的流行病学调查发现脓毒症的发病率大约是0．3％，所有患者中老年人的死亡率大约是30％～40％，而感染性休克患者的死亡率可高达50％以上。美国每年有75万脓毒症患者，约9％的脓毒症患者发展成重症脓毒症（severe sepsis），3％发展为脓毒性休克（septic shock），超过21万（28％）死亡，是ICU中主要的死亡原因。近年来，尽管早期积极地抗感染、液体复苏及相关脏器的功能支持，但总体病死率仍居高不下。因此对脓毒症流行病学调查研究有助于阐明其发病规律及影响因素，对指导临床治疗具有重要的意义。     

脓毒症患者中多重耐药鲍曼不动杆菌感染危险因素分析

目的 探讨综合重症监护病房（ICU）多重耐药（multi-drug resistant,MDR）鲍曼不动杆菌（Acinetobacter baumannii,Ab）感染脓毒症患者的临床特征和危险因素.方法 回顾分析2009年7月至2013年3月我院综合ICU入住脓毒症患者856例,通过比较多重耐药Ab感染脓毒症患者179例（病例组）与非多重耐药Ab感染脓毒症患者677例（对照组）的临床资料,探讨两组患者的病死率、住院费用、器官功能损害情况和死亡的危险因素.结果 多重耐药Ab感染脓毒症患者病死率、48 h病死率及住院费用较对照组高（P＜0.05）;多重耐药Ab感染脓毒症患者较对照组更易发生感染性休克、急性肾损伤和骨髓抑制;多重耐药Ab感染脓毒症患者如果APECHEⅡ评分＞25分、24 h内出现多脏器功能障碍综合征（MODS）、感染性休克,则其死亡风险更高（P＜0.05）.结论 多重耐药Ab感染脓毒症患者具有病死率高、治疗费用昂贵等特征,及时发现患者的死亡危险因素并进行针对性干预极其重要.     

烧伤早期严重感染集束治疗策略的应用

目的探讨严重感染集束治疗（SBT）策略在严重烧伤患者早期治疗中的实施情况及作用。方法95例重症烧伤患者,按治疗方式分为对照组43例和观察组52例。记录严重感染、感染性休克发生率、28d病死率和6h、24h集束治疗的依从率,logistic回归分析6h、24h集束治疗指标与感染、感染性休克发生及28d病死率的关系。结果观察组28天病死率、脓毒血症和感染性休克的发生率均明显低于对照组（P〈0．05）。早期目标导向液体治疗（EGDT）是烧伤感染和感染性休克发生的独立相关因素。血气分析测定、EGDT及血管活性药物的使用与28天病死率密切相关（P〈0．05）。烧伤感染、感染性休克的发生和28天病死率均与SBT方案的执行情况密切相关。观察组感染集束治疗指标的依从性仅为51．9％和63．2％。结论SBT方案能减少烧伤感染和感染性休克的发生,降低病死率,但依从性尚亟待提高。     

Eritoran: the evidence of its therapeutic potential in sepsis

Introduction:

Sepsis and its sequelae are the leading causes of morbidity and mortality in critically ill patients. The burden to healthcare economies is also considerable. As the pathophysiology of sepsis is better defined, interventions aiming to treat sepsis are emerging. Eritoran (E5564), a toll-like receptor 4 (TLR4)-directed endotoxin antagonist, is one such emerging therapeutic option for treatment of sepsis.

Aims:

This review assesses evidence for the potential therapeutic value of eritoran in the management of sepsis.

Evidence review:

Evidence from a single phase II trial of eritoran usage in sepsis suggests that it is a safe and effective therapeutic option for patients with sepsis, and is especially beneficial for patients at high risk of mortality. However, the cost effectiveness of eritoran and its place in therapy compared with other available treatment options and those currently in development remains to be determined.

Clinical potential:

Eritoran is a potential therapeutic option for management of sepsis and other TLR4- and lipopolysaccharide-mediated disorders with a reasonable safety and tolerability profile that must be validated by several rigorous, blinded, placebo-controlled, adequately powered, multicenter, randomized clinical trials.     

Immunosuppression in sepsis

The often fatal sepsis syndrome is characterized by the systemic release of inflammatory mediators, which is regulated and counterbalanced by the coordinated expression of anti-inflammatory molecules. The magnitude of sepsis-induced tissue injury and subsequent risk of infectious complications is dictated by the balance between the expression of pro- and anti-inflammatory mediators. As our understanding of the pathophysiology of sepsis continues to evolve, we have gained a greater appreciation for the profound effects that sepsis and similar states of overwhelming stress have on host innate and adaptive immunity. Impaired leukocyte function in sepsis has important clinical consequences, as high mortality rates have been observed in patients who display evidence of sepsis-induced immune dysregulation. Functional defects in leukocytes isolated from patients with sepsis include diminished expression of important cell surface molecules, dysregulated cytokine production, alterations in antigen-presenting ability, and accelerated apoptosis. In this article, we review the current literature supporting the notion that dysregulation of host immunity occurs during sepsis syndrome, and describe novel therapeutic interventions directed at augmenting host immunity during sepsis.     

Neonatal sepsis

A two year retrospective study of 242 neonates with a clinical diagnosis of neonatal sepsis was undertaken. The neonates on whom blood culture results were available for analysis were categorized into "proven" or "presumptive" sepsis. A changing pattern in aetiological pathogens is identified. The conspicuous absence of Group B Streptococcal (GBS) sepsis is discussed. The overall mortality rate was 37% but the mortality rate in the bacteraemic patients was only 22.6%. This discrepancy is discussed in detail and further prospective study suggested.     

Advantages and disadvantages of etomidate use for intubation of patients with sepsis

Etomidate is a potent imidazole hypnotic used widely in single doses in the rapid sequence intubation of critically ill patients with sepsis due to its presumed hemodynamic safety, fast onset, and short duration of action. However, the literature is conflicting regarding the hemodynamic advantages of etomidate over other induction agents, and its safety in this population is a matter of strong debate in the critical care community as the drug is associated with suppression of adrenal steroidogenesis, which can last up to 72 hours after a single dose, primarily through potent inhibition of the 11β-hydroxylase enzyme. However, the clinical impact of this adrenal suppressive effect is not certain. The use of continuous-infusion etomidate in critically ill patients was abandoned more than 20 years ago due to reports of increased mortality. Nevertheless, mortality data of single-dose etomidate are still controversial, with no strong evidence of benefit over other agents and a tendency toward harm (keeping in mind the limitations of the available literature). Proponents of single-dose etomidate use in patients with sepsis suggest that the increased mortality associated with etomidate is merely a reflection of the patients' severity of illness and not related to the drug itself, whereas others believe that the drug causes true harm and increases mortality in this population. In view of the lack of a clear clinical advantage of etomidate over other agents used in rapid sequence intubation, it would be prudent to favor other agents until further conclusive evidence of etomidate safety is available in critically ill patients with sepsis.     

Anti-inflammatory therapies in sepsis and septic shock

Despite advances in supportive care, the morbidity and mortality rate resulting from sepsis and septic shock remain high (30 - 50%). A central hypothesis driving sepsis research in recent years is that this syndrome is the result of excessive inflammation. Therapies designed to inhibit the inflammatory response were first shown to be markedly beneficial in animal models of sepsis and then tested in numerous clinical trials involving thousands of patients. Three broad anti-inflammatory strategies have been investigated. First, glucocorticoids in high doses administered at the onset of sepsis were studied. This approach proved unsuccessful. More recently, however, glucocorticoids in lower doses have been found to have a beneficial effect in patients with septic shock. Whether the mechanism of this treatment benefit is through inhibition of inflammation, or by counteracting a relative steroid refractoriness occurring during sepsis, remains unknown. The next focus of research were agents active against the endotoxin molecule. However, as with the experience with glucocorticoids, this approach lacked a consistent pattern of efficacy. It is unclear if this lack of efficacy is the result of endotoxin being a poor therapeutic target, or from testing agents which lacked the appropriate biological activity. Most recently, clinical trials in sepsis have focused on inhibiting specific host pro-inflammatory mediators (e.g., TNF, interleukins). While individual trials of inhibitors of these pro-inflammatory mediators failed to show a convincing benefit, pooling the results of these trials suggest that this approach has a marginal effect, supporting a role for excessive inflammation in sepsis. An unanswered question is reconcilling the very favourable effects obtained with anti-inflammatory treatments in animal models with the marginal results in humans. Further clinical and laboratory research is needed and may provide insight into more effective ways to use the anti-inflammatory agents already tested, or to investigate other potentially more effective anti-inflammatory agents in this syndrome.     

Anti-inflammatory therapies in sepsis and septic shock

Despite advances in supportive care, the morbidity and mortality rate resulting from sepsis and septic shock remain high (30 - 50%). A central hypothesis driving sepsis research in recent years is that this syndrome is the result of excessive inflammation. Therapies designed to inhibit the inflammatory response were first shown to be markedly beneficial in animal models of sepsis and then tested in numerous clinical trials involving thousands of patients. Three broad anti-inflammatory strategies have been investigated. First, glucocorticoids in high doses administered at the onset of sepsis were studied. This approach proved unsuccessful. More recently, however, glucocorticoids in lower doses have been found to have a beneficial effect in patients with septic shock. Whether the mechanism of this treatment benefit is through inhibition of inflammation, or by counteracting a relative steroid refractoriness occurring during sepsis, remains unknown. The next focus of research were agents active against the endotoxin molecule. However, as with the experience with glucocorticoids, this approach lacked a consistent pattern of efficacy. It is unclear if this lack of efficacy is the result of endotoxin being a poor therapeutic target, or from testing agents which lacked the appropriate biological activity. Most recently, clinical trials in sepsis have focused on inhibiting specific host pro-inflammatory mediators (e.g., TNF, interleukins). While individual trials of inhibitors of these pro-inflammatory mediators failed to show a convincing benefit, pooling the results of these trials suggest that this approach has a marginal effect, supporting a role for excessive inflammation in sepsis. An unanswered question is reconcilling the very favourable effects obtained with anti-inflammatory treatments in animal models with the marginal results in humans. Further clinical and laboratory research is needed and may provide insight into more effective ways to use the anti-inflammatory agents already tested, or to investigate other potentially more effective anti-inflammatory agents in this syndrome.     

The hypothalamic-pituitary-adrenal axis and low-dose glucocorticoids in the treatment of septic shock

Severe sepsis is the leading cause of death among patients in intensive care units. Recombinant activated protein C is the only substance known to directly improve morbidity and mortality. Adrenal insufficiency occurs frequently in patients with sepsis and is associated with poor outcome. Although high-dose glucocorticoids have not positively affected clinical outcome, small trials in which low-dose glucocorticoids were administered to patients with septic shock and relative adrenal insufficiency have shown decreased mortality. The main effect of glucocorticoids in low-doses apparently is exerted through correction of suppression of the hypothalamic-pituitary-adrenal axis. However, the therapeutic benefits of glucocorticoids may be related to their antiinflammatory properties and endogenous catecholamine-enhancing effects.     

Drotrecogin alfa (activated) in the treatment of severe sepsis

Severe sepsis and septic shock are common in the critically ill patient and account for considerable morbidity and mortality not to mention the high associated costs. Advances in our understanding of sepsis pathophysiology and in the important link between the inflammatory response to sepsis and activation of coagulation led to the development and licensing of the first ever, specific, immunomodulatory anti-sepsis drug. Drotrecogin alfa (activated), a recombinant version of activated protein C, was shown in a large randomized controlled clinical trial to reduce mortality rates from 30.8% in the placebo group to 24.7% in the treatment group, which equated to one additional life saved for every 16 patients treated. Vasopressor requirements and duration of mechanical ventilation were also reduced. Apart from an expected increased risk of severe bleeding, mostly associated with interventions, drotrecogin alfa (activated) was not associated with any other adverse reactions. In this article, I will briefly summarize the events leading to the development of drotrecogin alfa (activated) including aspects of sepsis epidemiology and pathophysiology and the results of early animal and clinical studies. The results of the large multicenter phase III PROWESS study will then be reviewed, along with results from subsequent open-label studies. Finally, I will focus on the key side effect issue with drotrecogin alfa (activated), that of increased bleeding, drawing data from the available clinical studies, and highlighting the contraindications and precautions when prescribing this drug.